Molecular Characterization of Factor VIII Gene Variants in Hemophilia A: A Genotype-Haplotype Study from Eastern and...

Hemophilia A is an X-linked recessive bleeding disorder caused by a deficiency or dysfunction of factor VIII (FVIII), affecting approximately 1 in 5,000 males globally, including those in northern India. Accurate carrier detection is vital for genetic counseling and early diagnosis. This study aimed to assess the allele frequencies of three key intronic polymorphisms-IVS7-SNP (G/A), rs4898352 (T/A) in intron 18 (Bcl-I), and rs4074307 (C/T) in intron 19 (Hind-III)-in Indian children with Hemophilia A and evaluate their utility in carrier detection and linkage analysis.

A total of 205 unrelated male children with Hemophilia A, representing 195 families from Eastern and Northern-Central India were included. Diagnosis was confirmed via FVIII assay. Genomic DNA was extracted from peripheral leukocytes. Genotyping of the three selected intronic polymorphisms in the F8 gene was carried out using ARMS-PCR.

The positive allele frequencies observed for IVS7-SNP, Bcl-I, and Hind-III were 0.10, 0.53, and 0.36, respectively. The negative allele of IVS7-SNP was found to be more prevalent among affected siblings. Family histories frequently revealed multiple affected individuals and hemophilia-related deaths, emphasizing the hereditary burden of the disorder in these regions.

The distribution of the studied polymorphisms is consistent with global heterozygosity patterns and underscores their potential role in carrier screening and linkage analysis. These findings provide a feasible genetic tool for early diagnosis and counseling in Hemophilia A, particularly in low-resource settings where direct mutation analysis is limited.